Our objective is to identify the extent to which neurohumoral control of the pulmonary circulation in conscious dogs is modified by an inhalational anesthetic (isoflurane) and a barbiturate (sodium pentobarbital). We will utilize a new technique which permits the generation of continuous multipoint pulmonary vascular pressure-flow (P:Q) plots in the conscious and anesthetized states. This technique avoids the limitations inherent in the use of single point calculations of pulmonary vascular resistance, and makes it possible to distinguish between active (vasoactive) and passive (flow-dependent) effects of physiological and pharmacological stimuli on the pulmonary circulation. Specific Aim 1 tests the hypothesis that anesthesia either directly or indirectly alters the baseline P:Q relationship during normoxia. Our preliminary data support this concept. Our previous and current work clearly indicates that the pulmonary circulation of conscious dogs is highly responsive to neurohumoral stimuli. Specific Aim 2 tests the hypothesis that anesthesia attenuates the pulmonary responses to exogenously administered and endogenously released neurohumoral stimuli. Specific Aim 3- 5 examine the effects of anesthesia on the pulmonary responses to 3 important reflexes that regulate the systemic circulation (baroreceptor, chemoreceptor and lung inflation reflexes). The pulmonary vascular effects of these reflexes have not been previously investigated in the conscious state. Specific Aim 3-5 test the hypothesis that activation of these 3 reflex pathways results in modulation of the pulmonary P:Q relationship in conscious dogs, and they additionally test the hypothesis that these reflex affects are attenuated during anesthesia. The roles of the autonomic nervous system, arginine vasopressin, and angiotensin II as efferent mechanisms mediating these pulmonary responses will also be investigated. The systematic evaluation of reflex neurohumoral control of the pulmonary circulation in chronically-instrumented conscious dogs will allow us to identify the specific effects of each anethetic agent without confounding influences of other anesthetics and acute surgical trauma. These studies should provide fundamental new information concerning vasoactive regulation of the pulmonary circulation in the conscious and anesthetized states, which should aid in the assessment and pharmacotherapy of patients undergoing surgical procedures that require anesthesia.